763 REGULATION OF D5 DOPAMINE RECEPTOR ON RENALASE EXPRESSION AND FUNCTION IN RAT RENAL PROXIMAL TUBULE CELLS

Abstract

Background: The dopaminergic and sympathetic systems interact to regulate blood pressure. Our previous studies show the regulation of dopamine receptor on α1-adrenergic receptor function. Due to the regulation of renalase on sympathetic tone, we hypothesize that dopamine receptor, especially D1-like receptor, might regulate renalase in kidney. Methods And Results: The effect of D1-like receptor on renalase expression and function was checked in immortalized renal proximal tubule (RPT) cells from Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHRs). It resulted that D1-like receptor agonist, fenoldopam increased renalase protein expression and function in WKY RPT cells, but decreased it in SHR cells. These effects were blocked by D1-like receptor antagonist SCH 23390. Fenoldopam increased renalase mRNA level in WKY RPT cells, but not in SHR cells. Fenoldopam increased the degradation of renalase protein in both WKY and SHR cells. However, the degradation degree was higher in SHR cells than in WKY cells. The regulation of D1-like receptor on renalase was mainly via D5 receptor, because D5 antisense blocked inhibitory effect of D1-like receptor on renalase in WKY cells. Moreover, PKC inhibitor 19-31 blocked the effect of fenoldopam on renalase expression; PKC agonist (PMA) inhibited renalase expression and function. Consistent with the in-vitro study, renalase expression was lower in kidney from SHRs than in WKY rats. Conclusions: The studies indicated that D1-like receptor, via D5 receptor, regulates renalase expression and function in RPT cells, aberrant regulation of D5 receptor on renalase might be involved in the pathogenesis of hypertension.